PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.
PQM-1 complements DAF-16 as a key transcriptional regulator of DAF-2-mediated development and longevity.
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DOI：
10.1016/j.cell.2013.07.006
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发表时间：
2013-08-01
期刊：
影响因子：
64.5
通讯作者：
Bussemaker HJ
中科院分区：
文献类型：
--
作者：
Tepper RG;Ashraf J;Kaletsky R;Kleemann G;Murphy CT;Bussemaker HJ
减少胰岛素/IGF-1样信号传导（IIS）延长C。通过依赖于保守的转录因子fos-16/FOXO的机制，通过上调应激反应（I类）和下调其他（II类）基因来延长线虫的寿命。通过整合全基因组mRNA表达的反应性，以在转录因子的纲要的全基因组的体内结合数据，我们发现，PQM-1是难以捉摸的转录激活因子，直接控制发育（II类）基因的结合到的β-16相关元件（DAE）。β-16仅通过β-16结合元件（DBE）直接调节I类基因。PQM-1的缺失抑制了daf-2的寿命，并进一步减缓了发育。令人惊讶的是，PQM-1和PQM-16的核定位是由IIS以相反的方式控制的，并且还被发现是相互拮抗的。我们观察到随着年龄的增长，核PQM-1的逐渐丧失，解释了PQM-1靶点表达的下降。总之，我们的数据表明了一种平衡压力反应和发展的优雅机制。
Reduced insulin/IGF-1-like signaling (IIS) extends C. elegans lifespan by upregulating stress response (Class I) and downregulating other (Class II) genes through a mechanism that depends on the conserved transcription factor DAF-16/FOXO. By integrating genomewide mRNA expression responsiveness to DAF-16 with genomewide in vivo binding data for a compendium of transcription factors, we discovered that PQM-1 is the elusive transcriptional activator that directly controls development (Class II) genes by binding to the DAF-16 associated element (DAE). DAF-16 directly regulates Class I genes only, through the DAF-16 binding element (DBE). Loss of PQM-1 suppresses daf-2 longevity and further slows development. Surprisingly, the nuclear localization of PQM-1 and DAF-16 is controlled by IIS in opposite ways, and was also found to be mutually antagonistic. We observe progressive loss of nuclear PQM-1 with age, explaining declining expression of PQM-1 targets. Together, our data suggest an elegant mechanism for balancing stress response and development.
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影响因子：
3.7
作者：
Boorsma, Andre;Lu, Xiang-Jun;Zakrzewska, Anna;Klis, Frans M.;Bussemaker, Harmen J.
通讯作者：
Bussemaker, Harmen J.
影响因子：
64.5
作者：
Budovskaya YV;Wu K;Southworth LK;Jiang M;Tedesco P;Johnson TE;Kim SK
通讯作者：
Kim SK
影响因子：
3.9
作者：
Murphy, Coleen T.
通讯作者：
Murphy, Coleen T.
影响因子：
7.8
作者：
McElwee, J;Bubb, K;Thomas, JH
通讯作者：
Thomas, JH
全基因组DFOXO靶标和对压力和胰岛素信号转导的转录组响应的拓扑。
影响因子：
9.9
作者：
Alic, Nazif;Andrews, T. Daniel;Giannakou, Maria E.;Papatheodorou, Irene;Slack, Cathy;Hoddinott, Matthew P.;Cocheme, Helena M.;Schuster, Eugene F.;Thornton, Janet M.;Partridge, Linda
通讯作者：
Partridge, Linda